Biomedical research forms the basis of evidence based practices in the
field of health and nutrition. However, it is, increasingly being seen
that conflicts of interest and misconduct are undermining research. More
and more instances of using research to promote commercial interest are
being reported. Fraudulent means, in the quest to publish, are also
being used. This article discusses conflict of interest and misconduct
in bio-medical research, reviews scientific evidence available on the
subject, and proposes some solutions to check the menace.

Each year, hundreds of biomedical journals
across the world publish innumerable research papers. Based on this
research, clinical guidelines are prepared to guide experts,
governments and implementing agencies. Biomedical research also
feeds the judicious use of current best evidence in making patient
care decisions [1,2]. Notwithstanding the importance of the
biomedical research, it is imperative that it remains impartial,
free from fraud, misconduct and conflict of interest.

Conflict of interest: (COI) in the
biomedical research is defined as "a set of conditions in
which professional judgment concerning a primary interest
(such as patients’ welfare or the validity of research)
tends to be unduly influenced by a secondary interest (such
as financial gain)" [3].

Financial conflict of interest is a condition and
not a behaviour and therefore, circumstances determine presence or
absence of conflict of interest [3,4]. The International Committee
of Medical Journal Editors (ICMJE) form for disclosure of potential
conflicts of interest requires information from the researchers
about the work under consideration for publication like receiving
grant, consulting fee or honorarium, payment for writing or
reviewing the manuscript etc.; and information about the relevant
financial activities outside the submitted work including board
membership, consultancy, payment for lectures including service on
speakers bureaus [5].

It is worth noting that academic–industry
relationships have been an essential

component of research enterprise in the life
sciences. Empiricaldata
show that more than half of academic scientists have suchrelationships, which most often involve
consulting, receiving
research funding, and providing scientific advice [6]. Whether the
scenario is similar in India, is difficult to judge from the
literature.

Fraudulent research includes fabrication,
falsification or modification of data or results. Research
misconduct, which may be detrimental to patients, also damage public
trust in science [7]. In a survey of more than 2700 researchers, one
in seven UK based scientists or doctors had witnessed colleagues’
intentionally altering or fabricating data during their research or
for the purposes of publication [8].

Various agencies have outlined ethical codes of
conduct to carry out and report research [9]. The question is, can
vested interests manipulate these norms to their own advantage
rather than for the public good? Can there be a bias in favour of
those who are funding the research? Can guideline developing bodies
be affected by unrecognised extraneous interests? This article is an
attempt to explore some of these issues.

Anatomy of Research Funding - Who is Setting
Agenda for the Biomedical Research?

To understand the issue of COI and misconduct in
biomedical research, it is important to explore the anatomy of
research funding. Worldwide about $56bn [(£37.3bn) per year was
spent on health research by both the public and private sectors
[10]. The Global Forum for Health Research estimated a decade ago
that less than 10% of research funds were spent on the diseases that
account for 90% of the global burden of disease. The funding of
research studies by the industry, with explicit or implicit conflict
of interest has been a growing trend. A recent review concluded that
author conflict of interest in psychiatric clinical trials was
associated with

a
greater likelihood of reporting a drug to be superior to placebo
[11].

A study, which analyzed research papers published
in New England Journal of Medicine and Journal of American Medical
Association, found that private corporations funded approximately
one third of original manuscripts published in these journals [12].
The study also found that around 30% articles had one or more
authors with a conflict of interest. Interestingly, authors with
conflicting interest were 10 to 20 times less likely to present
negative findings than those without COI. The fact that negative
findings were less commonly reported by the authors having COI
raises serious ethical questions [12]. Since such research is
conducted in collaboration with prestigious researchers, institutes
and even government agencies, very few questions are probably asked
even by the editors.

Another issue with far-reaching implications is
the choice of

topics and
the direction of research. A survey of over 1,200 faculty members at
40 major US universities about research activities and funding
revealed that commercial considerations have at one time or other
influenced their choice of research projects [13].

In spite of the widespread concerns about the
conflict of interest in research, some researchers do not find it
troublesome and felt that it is a lot of fuss about nothing [14]. An
editor of a journal, dismissed objections about the infant formula
companies sponsoring research in the field of infant nutrition,
saying that people who are raising such objections have scanty
scientific-epidemiological evidence, together with

a most unwelcome emotional component [14]. One
researcher, whose many studies were sponsored by the formula
industry, has stressed for a close collaboration between responsibleclinical scientists and industry as research
in infant nutrition requires substantial investment [16].

These arguments are now becoming steadily less
tenable as evidence accumulates on the influence of conflict of
interest [14]. As per Rundall [17], "Companies - especially those
that are the subject of criticism - have a particular need to offer
sponsorship, knowing that it

works on many levels. Without it, companies find it
much harderto silence
potential critics; create the image that they are responsible"corporate citizens" who can be trusted to
regulate themselves;
influence public health policies and priorities; link their nameto prestigious non-governmental organisations,
United Nationsagencies,
and health professionals; affect the direction and outcome of
research;create
dependency; and create public confusion about the real causesof poverty" [17].

Disclosure of Funding From Industry

To address the great variability in the processes
that different journals use to ask about and report authors’
potential conflicts of interest, the International Committee of
Medical Journal Editors [ICMJE] developed an electronic uniform
disclosure form in 2009, which was piloted by ICMJE member journals
[5] and since than being used by many international scientific
journals. Such modalities, even if diligently adhered to; ultimately
leave the onus of judging the veracity of the research findings on
the reader, who may sometimes fail to take note of the conflict of
interest. An analysis of conflict of interest policies of medical
journals has revealed that most journals’ COI definitions were
limited

to direct
financial interests only and there was a discrepancy between
journalshaving COI
policies (89%) and those requiring signed statements (54%) from each
author [18].

A study to look at information on ethics
reporting and authorship in the "instructions to authors" section of
59 Indian medical journals found that guidance regarding ethics was
mentioned in 43 (72.8%) journals; and authorship criteria were
mentioned in 38 (64.5%) journals [19]. Authorship criteria according
to the International Committee of Medical Journal Editors were
mentioned only in 35 (59.3%) journals and guidance regarding
contributors’ details was mentioned only in 30 (50.8%) journals
[19]. These findings suggest that in spite of so much concern about
the issue of conflict of interest in the reported research, not many
journals in India enforce strict criteria for authors to include
ethical requirements. A survey of 221 North American medical journal
editors also found that only 26% required authors to reveal their
funding sources [20] and in a large number of pharmacoeconomic
studies funding sources are not specified [21]. Two older studies
also report similar data from the US [19,20]. It is also often seen
that ties between researchers and industry are omitted from media
reports about drugs [22].

Misconduct in Clinical Trials

Health and nutrition industry including drug and
infant formula companies have been able to create a scientific
environment which helps them to promote their products to the
unsuspecting consumers. They are being knowingly or unknowingly
getting support from researchers, funding agencies and scientific
journals. There is an inherent conflict of interest in such
collaborations, where the company strives to advance its interests
by controlling the scientific agenda and focusing

on product development [23].

Motivated and fraudulent research

There are examples of misconduct by researchers
in the conducting of research or reporting of results. There are
instances, when both false results and conclusions were reported or
some important negative facts were suppressed. Some examples are
given below.

In 2005, the journal Nutrition retracted a
paper by a Canadian researcher about effect of vitamin and
trace-element supplementation on cognitive function in elderly
subjects [24], as the author failed to give an adequate response to
the questions asked by the journal about the research findings [25].
The research claimed to be a randomized double blind placebo
controlled trial concluded that physiological amounts of vitamins
and trace elements could improve cognitive function in elderly
people. This paper had been initially submitted to the British
Medical Journal, which had rejected it due to doubts about the
paper [26]. In fact, one of the reviewers had opined that the paper
"had all the hallmarks of having been entirely invented" [26]. Apart
from having concerns related to the veracity of the data, the author
also held a patent for the nutritional supplement that was claimed
to improve cognition, thus, clearly reflecting a COI. Further to
this, the Canadian Broadcasting Corporation investigated the past
research works of the scientist and found that he indulged in
fraudulent research on hypoallergenic formula also. His research
studies, which were supported by the formula manufacturers (Nestle,
Mead Johnson), concluded that the products were hypoallergenic [27].
It is important to note here that armed with the ‘scientific
evidence’ provided by the ‘research’ mentioned above, one of the
company which sponsored the research, promoted its’ product among
the public for years to create a market for the product and convince
medical professionals with claims about protection against allergy
[28].

One more example of manipulated research is
studies on the anti-hyperglycemic drug Rosiglitazone. After being in
use for many years, research suggested that Rosiglitazone carried
cardiovascular risks [29,30]. A post-marketing surveillance funded
by the manufacturer of the drug (GlaxoSmithKline plc UK), concluded
that addition of rosiglitazone to glucose-lowering therapy in people
with type 2 diabetes is confirmed to increase the risk of heart
failure [31]. The United States Senate Committee on Finance,
suggested that excess cardiovascular events with the drug appeared
as early as 2004, but that the manufacturer, GlaxoSmithKline (GSK),
intimidated researchers and manipulated the scientific process for
commercial advantage [32,33]. Further, a systematic review on
rosiglitazone and the risk of

myocardial infarction found that articles thatgave a favorable view on the risks were
significantly more
likely to have authors with financial ties to the manufacturersof anti-hyperglycemic agents in general, and
rosiglitazone in
particular, than those with unfavorable views [34].

Ghost writing and guest authorship

Guest authorship is the practice of publishing
studies prepared by hired medical writers but signed by academic
"guest authors" who are invited to add their names without
fulfilling authorship criteria. Sometimes, "guest authorship" is
accompanied by "ghostwriting," which occurs when a published article
fails to acknowledge the original writer or writers’ contributions.
Ghostwriting of medical journal articles raises serious ethical and
legal concerns, bearing on the integrity of medical research and
scientific evidence used in legal disputes [35].It has been reported
that clinical trial manuscripts related to a drug were authored by
sponsor employees but first authorship was attributed to
academically affiliated investigators who did not always disclose
industry financial support. Similar authorship patterns had happened
in the review manuscripts [36].

Conflict of Interest in Drafting Policies and
Clinical Guidelines

Research findings are ultimately used to
formulate policies and clinical guidelines. Potential conflict of
interest due to involvement of scientists and researchers with
financial ties with industry in global and local policy making is a
major issue. COIs can arise through authors having financial links
with industry, including being paid consultancies or honoraria, or
holding company shares [37]. During the recent pandemic flu,
investigations revealed that key scientists advising the World
Health Organization on planning for an influenza pandemic had done
paid work for pharmaceutical firms that stood to gain from the
guidance they wrote. These conflicts of interest have never been
publicly disclosed by WHO [38].

Similarly, a study of 313 Australian clinical
guidelines used between 2003 and 2007 found that only 15% of
guidelines on the National Health and Medical Research Council
portal from the most prolific developers have published conflict of
interest statements, and fewer detail the processes used to manage
conflicts [39]. A cross sectional study to determine the prevalence
of financial conflict of interest among members of panels to develop
clinical guidelines for diabetes and hyperlipidemia found that out
of 288 panel members, 52% had had conflicts [37]. Interestingly, it
was revealed that panel members from government sponsored guidelines
were less likely to have conflicts of interest compared with
guidelines sponsored by non-government sources [40].

Review articles are widely used to draft policies
and formulate guidelines. It has been shown that the conclusions of
review articles are strongly associated with the affiliations of
their authors. Of 106 reviews on the health effects of passive
smoking, 37% (39/106) concluded that passive smoking is not harmful
to health; 74% (29/39) of these were written by authors with tobacco
industry affiliations. In multiple logistic regression analyses
controlling for article quality, peer review status, article topic,
and year of publication, the only factor associated with concluding
that passive smoking is not harmful was whether an author was
affiliated with the tobacco industry [41].

Conclusions

Biomedical research is crucial to practice
evidence based medicine. Hence, it is essential to keep it’s
sanctity maintained [Box I]. It is evident that
scientific tools like biomedical research may be used by the market
forces as a medium to gain profits. Medical professionals, policy
makers, UN agencies and media should observe due diligence while
using research conclusions for public health recommendations,
keeping in view the conflict of interest on part of the authors. At
the same time, there is a need to find some mechanism in the editing
process by the journals to identify the conflict of interest and to
notify it to the readers in a more explicit manner.

Box I Interventions Suggested as a
Safeguard Against Misconduct in Biomedical Research

1. Public funding of the biomedical
research: Public funding for the basic and core health
issues, including intervention operational studies,
according to the needs of the country should be enhanced and
made available to agencies without any conflict of interest.

2. Regulatory system for financial
support and publications of research: To improve the
system to effectively regulate and oversee researchers and
journals and to improve the current financial disclosures
regulations, we need to enforce a system to regulate
financing of the biomedical research studies and publication
of research articles. Search engines like PubMed should
adopt a mechanism to highlight conflict of interests also
with the abstracts and summaries.

3. Trial Registry: The issue of
selective reporting of the positive and suitable results
could be tackled with establishment of trial registry at
national and international level. It also helps in bringing
a balance to the available evidence by making available both
negative as well as positive results. At international
level, the WHO International Clinical Trials Registry
Platform (ICTRP) has been established [42]. In India, The
Clinical Trials Registry- India (CTRI) has been established
by the ICMR. The Drugs Controller General (India) has made
it mandatory for all the drug trials being conducted in
India to get registered with CTRI [43].

4. Careful scrutiny of scientific
studies quoted for the health claims by the industry:
Regulatory provisions should be in place to examine the
health claims and the supporting research for a nutritional
or pharmaceutical product by the industry.

5. Effective code of conduct for
guidelines and policy panels: All the experts
participating in the guidelines and policy panels should
submit a COI statement, which should be published alongwith
the guidelines.

6. Definitive punitive action for misconduct in
research and fraudulent research: Regulatory bodies for
clinical research and Academic institutions should have a
protocol in place for appropriate action for research
misconduct.

32. The United States Senate Committee on
Finance. Grassley, Baucus release committee report on Avandia.
Available at:
http://finance.senate.gov/newsroom/chairman/release/?id=bc56b552-efc5-4706-968d-f7032d5cd2e4.
Accessed on April 25, 2012.